ION SELECTIVITY PREDICTIONS FROM A 2-SITE PERMEATION MODEL FOR THE CYCLIC NUCLEOTIDE-GATED CHANNEL OF RETINAL ROD CELLS

We developed a two-site, Eyring rate theory model of ionic permeation for cyclic nucleotide-gated channels (CNGCs). The parameters of the mo del were optimized by simultaneously fitting current-voltage (IV) data sets from excised photoreceptor patches in electrolyte solutions cont aining one or more of the following ions: Na+, Ca2+, Mg2+, and K+. The model accounted well for 1) the shape of the IV relations; 2) the bin ding affinity for Na+; 3) reversal potential values with single-sided additions of Ca2+ or Mg2+ and biionic KCI; and 4) the K-i and voltage dependence for divalent block from the cytoplasmic side of the channel . The differences between the predicted K-i's for extracellular block by Ca2+ and Mg2+ and the values obtained from heterologous expression of only the alpha-subunit of the channel suggest that the beta-subunit or a cell-specific factor affects the interaction of divalent cations at the external but not the internal face of the channel. The model p redicts concentration-dependent permeability ratios with single-sided addition of Ca2+ and Mg2+ and anomalous mole fraction effects under a limited set of conditions for both monovalent and divalent cations. Ca 2+ and Mg2+ are predicted to carry 21% and 10%, respectively, of the t otal current in the retinal rod cell at -60 mV.